RESUMO
Recently, the role of exosomes in the progression of both cancer and HIV (human immunodeficiency virus) has been described. This study investigates the clinical significance of CD9-positive plasma exosomes in lung cancer patients, healthy individuals, and HIV-positive patients with or without lung cancer. Using a verified with transmission electron microscopy double-sandwich ELISA technique, plasma-derived exosomes were isolated and quantified from 210 lung cancer patients (including 44 metastatic patients with progressive disease after chemotherapy), 49 healthy controls, 20 patients with pulmonary granulomas, 19 HIV+ patients with lung cancer, 31 HIV+ patients without cancer, and 3 HIV+ patients with pulmonary granulomas. Plasma exosome concentrations differed between healthy controls, patients with immunocompetent pulmonary granulomas and patients with lung cancer even after chemotherapy (p < 0.001). Lung cancer patients after chemotherapy had lower exosome concentrations compared to patients with untreated lung cancer or granuloma (p < 0.001 for both). HIV+ patients without lung cancer had significantly higher exosome concentrations compared to HIV+ patients with lung cancer (p = 0.016). Although exosome concentrations differed between all different lung cancer histologies and healthy controls (p < 0.001 for all histologies), adjusted statistical significance was oµy retained for patients with granulomas and SCLC (Small-cell lung cancer, p < 0.001). HIV-induced immunodeficient patients with or without lung cancer had lower plasma exosomes compared to immunocompetent granuloma and lung cancer patients (p < 0.001). Finally, higher plasma exosomes were associated both on univariate (p = 0.044), and multivariate analysis (p = 0.040) with a better 3-year survival in stage II and III NSCLC (Non-small-cell lung carcinoma) patients. In conclusion, our study shows that CD9-positive plasma exosomes are associated with both lung cancer and HIV, prior chemotherapy, as well as with survival, suggesting a possible prognostic value.
RESUMO
Lung cancer is the leading cause of death from cancer worldwide that currently has only a few available treatment options in patients with no driver mutations. The therapeutic options for patients with non-small-cell lung cancer (NSCLC) who progress after first-line chemotherapy have been limited from a long time. Docetaxel has remained a cornerstone of second-line treatment for more than 20 years, but it is associated with an unfavorable safety profile. Recently, the results from immunotherapy treatment with anti-PD1 and PD-L1 inhibitors has changed our current knowledge base and increased therapeutic options for patients with NSCLC in the second-line setting. The results of 2 randomized phase III trials assessing nivolumab in lung cancer, Check-Mate-017 and Check-Mate-057, have deeply changed our current clinical practice and raised several discussion points. This paper explores the recent findings about nivolumab for the treatment of NSCLC in the second-line setting by analyzing recent trial findings and discussing their implications in clinical practice and future directions. The paper also summarizes the conclusions from an International Experts Panel Meeting of the Italian Association of Thoracic Oncology.